Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: identification of new mutations
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2011 |
| Outros Autores: | , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/17633 |
Resumo: | Acesso aberto na Internet Janeiro 2017 |
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Coelho, Millene BorgesDalla Costa, Elis ReginaVasconcellos, Sidra Ezídio GonçalvesLinck, NataliRamos, Ricardo MartinsAmorim, Hermes Luís Neubauer deSuffys, Philip NoelSantos, Adalberto RezendeSilva, Pedro Eduardo Almeida daRamos, Daniela FernandesSilva, Márcia Susana NunesRossetti, Maria Lucia Rosa2017-01-31T13:02:48Z2017-01-31T13:02:48Z2011COELHO, Millene Borges; et al. Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: Identification of new mutations. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, v.712, n.1–2, p.33–39, July 2011.0027-5107https://www.arca.fiocruz.br/handle/icict/1763310.1016/j.mrfmmm.2011.03.017Acesso aberto na Internet Janeiro 2017Universidade Luterana do Brasil (PPGGTA/ULBRA). Programa de Pós-Graduação Em Genética Aplicada e Toxicologia. Canoas, RS, Brasil.Fundação Estadual de Produção e Pesquisa em Saúde. Centro de Desenvolvimento Científico e Tecnológico (CDCT/FEPPS). Porto Alegre, RS, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada em Micobactérias. Rio de Janeiro, RJ. Brasil.Universidade Luterana do Brasil (PPGGTA/ULBRA). Programa de Pós-Graduação Em Genética Aplicada e Toxicologia. Canoas, RS, Brasil.Universidade Luterana do Brasil (PPGGTA/ULBRA). Programa de Pós-Graduação Em Genética Aplicada e Toxicologia. Canoas, RS, Brasil.Universidade Luterana do Brasil (PPGGTA/ULBRA). Programa de Pós-Graduação Em Genética Aplicada e Toxicologia. Canoas, RS, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada em Micobactérias. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada em Micobactérias. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio Grande do Sul. Faculdade de Medicina. Laboratório de Micobactéria. Porto Alegre, RS, Brasil.Universidade Federal do Rio Grande do Sul. Faculdade de Medicina. Laboratório de Micobactéria. Porto Alegre, RS, Brasil.Universidade Luterana do Brasil (PPGGTA/ULBRA). Programa de Pós-Graduação Em Genética Aplicada e Toxicologia. Canoas, RS, Brasil / Fundação Estadual de Produção e Pesquisa em Saúde. Centro de Desenvolvimento Científico e Tecnológico (CDCT/FEPPS). Porto Alegre, RS, Brasil.Universidade Luterana do Brasil (PPGGTA/ULBRA). Programa de Pós-Graduação Em Genética Aplicada e Toxicologia. Canoas, RS, Brasil / Fundação Estadual de Produção e Pesquisa em Saúde. Centro de Desenvolvimento Científico e Tecnológico (CDCT/FEPPS). Porto Alegre, RS, Brasil.The present study was carried out to investigate the presence of polymorphism in the N-acetyltransferase gene of 41 clinical isolates of Mycobacterium tuberculosis, that were resistant to isoniazid (INH) with no mutations in the hot spots of the genes previously described to be involved in INH resistance (katG, inhA and ahpC). We observed single nucleotide polymorphisms (SNPs) in ten of these, including the G619A SNP in five isolates and an additional four so far un-described mutations in another five isolates. Among the latter SNPs, two were synonymous (C276T, n=1 and C375G, n=3), while two more non-synonymous SNPs were composed of C373A (Leu→Met) and T503G (Met→Arg) were observed in respectively one and two isolates. Molecular modeling and structural analysis based in a constructed full length 3D models of wild type TBNAT (TBNAT_H37Rv) and the isoforms (TBNAT_L125M and TBNAT_M168R) were also performed. The refined models show that, just as observed in human NATs, the carboxyl terminus extends deep within the folded enzyme, into close proximity to the buried catalytic triad. Analysis of tbnat that present non-synonymous mutations indicates that both substitutions are plausible to affect enzyme specificity or acetyl-CoA binding capacity. The results contribute to a better understanding of structure-function relationships of NATs. However, further investigation including INH-sensitive strains as a control group is needed to get better understanding of the possible role of these new mutations on tuberculosis control.engElsevierMycobacterium tuberculosisResistência a medicamentosModelagem molecularEstrutura-funçãoMutaçãoMutationStructure–functionDrug resistanceMolecular modelingMycobacterium tuberculosisSequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: identification of new mutationsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; 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| dc.title.pt_BR.fl_str_mv |
Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: identification of new mutations |
| title |
Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: identification of new mutations |
| spellingShingle |
Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: identification of new mutations Coelho, Millene Borges Mycobacterium tuberculosis Resistência a medicamentos Modelagem molecular Estrutura-função Mutação Mutation Structure–function Drug resistance Molecular modeling Mycobacterium tuberculosis |
| title_short |
Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: identification of new mutations |
| title_full |
Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: identification of new mutations |
| title_fullStr |
Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: identification of new mutations |
| title_full_unstemmed |
Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: identification of new mutations |
| title_sort |
Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: identification of new mutations |
| author |
Coelho, Millene Borges |
| author_facet |
Coelho, Millene Borges Dalla Costa, Elis Regina Vasconcellos, Sidra Ezídio Gonçalves Linck, Natali Ramos, Ricardo Martins Amorim, Hermes Luís Neubauer de Suffys, Philip Noel Santos, Adalberto Rezende Silva, Pedro Eduardo Almeida da Ramos, Daniela Fernandes Silva, Márcia Susana Nunes Rossetti, Maria Lucia Rosa |
| author_role |
author |
| author2 |
Dalla Costa, Elis Regina Vasconcellos, Sidra Ezídio Gonçalves Linck, Natali Ramos, Ricardo Martins Amorim, Hermes Luís Neubauer de Suffys, Philip Noel Santos, Adalberto Rezende Silva, Pedro Eduardo Almeida da Ramos, Daniela Fernandes Silva, Márcia Susana Nunes Rossetti, Maria Lucia Rosa |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Coelho, Millene Borges Dalla Costa, Elis Regina Vasconcellos, Sidra Ezídio Gonçalves Linck, Natali Ramos, Ricardo Martins Amorim, Hermes Luís Neubauer de Suffys, Philip Noel Santos, Adalberto Rezende Silva, Pedro Eduardo Almeida da Ramos, Daniela Fernandes Silva, Márcia Susana Nunes Rossetti, Maria Lucia Rosa |
| dc.subject.other.pt_BR.fl_str_mv |
Mycobacterium tuberculosis Resistência a medicamentos Modelagem molecular Estrutura-função Mutação |
| topic |
Mycobacterium tuberculosis Resistência a medicamentos Modelagem molecular Estrutura-função Mutação Mutation Structure–function Drug resistance Molecular modeling Mycobacterium tuberculosis |
| dc.subject.en.pt_BR.fl_str_mv |
Mutation Structure–function Drug resistance Molecular modeling Mycobacterium tuberculosis |
| description |
Acesso aberto na Internet Janeiro 2017 |
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2011 |
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2011 |
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2017-01-31T13:02:48Z |
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2017-01-31T13:02:48Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.citation.fl_str_mv |
COELHO, Millene Borges; et al. Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: Identification of new mutations. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, v.712, n.1–2, p.33–39, July 2011. |
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https://www.arca.fiocruz.br/handle/icict/17633 |
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0027-5107 |
| dc.identifier.doi.none.fl_str_mv |
10.1016/j.mrfmmm.2011.03.017 |
| identifier_str_mv |
COELHO, Millene Borges; et al. Sequence and structural characterization of tbnat gene in isoniazid-resistant Mycobacterium tuberculosis: Identification of new mutations. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, v.712, n.1–2, p.33–39, July 2011. 0027-5107 10.1016/j.mrfmmm.2011.03.017 |
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eng |
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Elsevier |
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Elsevier |
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